核受体LXR促进BATF2表达的分子机制及其在抗肝细胞癌中的作用研究

AP-1, an important tumor suppressor, can significantly repress HCC cell poliferation. LXR, as a transcription factor with multiple functions, is found to be a new tumor suppressor, but its molecular mechanism is not clear. In the preliminary research, we firstly showed that LXR activation dramatically induced BATF2 expression in HCC cells , and report assay showed that potential LXR binding sites existed in 5’ regulatory region of BATF2 gene. Therefore we suppose that “BATF2 is a new target gene of LXR and‘LXR-BATF2 pathway’ may be the new mechanism by which LXR represses HCC cell poliferation”. For the further research, we will find out the molecular mechanism through which LXR upregulates BATF2 using a series of technologies such as EMSA, ChIP. Subsequently, Flow cytometry assay, cell poliferation tests, RNAi, experiments in vivo on nude mice and so on will be exerted to show the important role of “LXR-BATF2 pathway” in anti-HCC progress. All above, our research will reveal that LXR is a significant regulator of BATF2 and put a new insight into the search for novel therapeutic strategy for HCC by targeting “LXR-BATF2 pathway”.

AP-1强效抑制分子(BATF2)是重要的抗肿瘤分子，能明显抑制HCC细胞增殖。核受体LXR是一种多效转录因子，近年发现抗肿瘤是其一项新的重要功能，但机制尚不清楚。本项目在前期研究中，率先发现在HCC细胞中LXR活化能明显促进BATF2表达；报告基因检测显示在BATF2的5＇调控区存在LXR潜在结合位点，因此我们提出假设“BATF2极有可能是LXR的一个新靶基因，‘LXR-BATF2信号通路’很有可能是LXR发挥抗HCC作用的新机制”。基于此，我们拟借助EMSA、ChIP等实验，阐明LXR促进BATF2表达的分子机制，明确BATF2是LXR的一新靶分子；经流式细胞检测、细胞凋亡检测等体外实验以及建立肝癌荷瘤鼠模型等体内实验观察LXR对BATF2表达的调节，初步揭示LXR促进BATF2表达在抗HCC中的作用，从而为深入研究以“LXR-BATF2信号通路”为靶标的抗HCC新策略提供科学依据。

AP-1强效抑制分子(BATF2)是重要的抗肿瘤分子，能明显抑制HCC细胞增殖。核受体LXR是一种多效转录因子，近年发现抗肿瘤是其一项新的重要功能，但机制尚不清楚。本项目研究中，率先发现在HCC细胞中LXR活化能明显促进BATF2表达；报告基因检测显示在BATF2的5＇调控区存在LXR潜在结合位点，并且活化LXR后，BATF2的下游靶基因CD1、CCN1、VEGF能在mRNA水平和蛋白水平被明显下调。这些结果提示“LXR-BATF2”通路可能是通过细胞周期阻滞、抑制细胞侵袭和肿瘤血管生成等来抑制肝细胞的进展。总之，我们的研究表明“BATF2极有可能是LXR的一个新靶基因，‘LXR-BATF2信号通路’很有可能是LXR发挥抗HCC作用的新机制”。